Project/Area Number |
04670531
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Shiga University of Medical Science |
Principal Investigator |
KINOSHITA Masahiko Shiga University of Medical Science First Iternal Medicine Professor, 医学部, 教授 (60093168)
|
Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Yishihisa Shiga University of Medical Science First Iternal Medicine Assistant Professor, 医学部, 助手 (30216337)
TSUTAMOTO Takayoshi Shiga University of Medical Science First Iternal Medicine Assistant Professor, 医学部, 助手 (40197695)
|
Project Period (FY) |
1992 – 1993
|
Project Status |
Completed (Fiscal Year 1993)
|
Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
Keywords | coronary artery / phasic contraotion / K^+ channel / glibenclamide / グリベンクラシド / グリハツクラミド |
Research Abstract |
To investigate the role of ATP-sensitive potassium chammel (ATP-K) in coronary arteries, we examined the effects of intravenous administration of glibenclamide (GLB, 0.3, 1.0, 3.0 mg/kg), a specific ATP-K blocker, in chronically instrumented dogs. Epicardial coronary artery diameter(CoD) and coronary blood flow (CBF) were measured continuously. Oscillations of CoD and CBF (phasic contractions) accurred in all of 6 dogs after injection of GLB (3mg/kg). CoD oscillated only slightly with a decrease by 2.3(〕SY.+-.〔)0.4 % ; CBF showed marked oscillation, with a peak flow rate of 21.9(〕SY.+-.〔)2.7ml/min(+26.6%) and atrough flow rate of 10.3(〕SY.+-.〔)2.9ml/min(-46.3%) (baseline flow was 17.8(〕SY.+-.〔)2.4 ml/min). GLB (1mg/kg) produced a slight decrease in CBF without oscillation, while GLB (0.3mg/kg)had almost no effect. These oscillations were not associated with a decrease in myocardial blood flow by the hydrogen gas clearance method. Nicrandil(0.2mg/kg), cromakalim (20 mug/kg) and diltiazem (0.2mg/kg) almost completely suppressed the oscillation, while nitroglycerin (15 mug/kg) did not. These findings suggest that ATP-K has an important in vivo role in modulating large and small coronary artery tone through activation of the voltage-dependent Ca channel.
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